Implication of peroxisome proliferator-activated receptor γ and proinflammatory cytokines in gastric carcinogenesis: Link to Helicobacter pylori-infection

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor involved in various processes including the inflammation and carcinogenesis. The aim of the present study was 1) to examine the mRNA and protein expression of PPARγ in gastric cancer (GC); 2) to evaluate the effect of PPARγ ligand (ciglitazone) on the proliferation and apoptosis of GC cell line; and 3) to assess the levels of gastric tissue proinflammatory cytokines, IL-1β and IL-8, and plasma gastrin in GC patients before and after Helicobacter pylori (H. pylori) eradication. The trial material included 30 H. pylori-negative controls and 30 sex- and age-matched GC patients without or with H. pylori before and after its eradication. Expression of tissue PPARγ, tissue levels of IL-1β and IL-8, and plasma concentration of gastrin were significantly higher in H. pylori-positive GC-compared to controls, but H. pylori eradication significantly reduced these parameters. Kato III cells incubated with alive H. pylori upregulated PPARγ expression and ciglitazone inhibited cells proliferation and induced apoptosis. PPARγ, proinflammatory cytokines and plasma gastrin appear to be implicated in H. pylori-related gastric carcinogenesis and PPARγ agonists may have potential in cancer therapy.